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Biomedical subjects

J D'Agostino

Publications and source records attributed to J D'Agostino.

At least 19 recordsLinked to original sources
PubMed2005

Influence of atrial fibrillation on cardiac brain natriuretic peptide release during haemodynamic stress in heart failure.

BACKGROUND: The determinants of release of brain natriuretic peptide (BNP) in heart failure (HF) are incompletely understood, particularly, the effect of heart rhythm and haemodynamic stress. AIMS: To investigate the effect of haemodynamic stress on cardiac BNP release in HF and differentiate this response for atrial fibrillation (AF) and sinus rhythm (SR). METHODS: In 18 HF patients (ejection fraction<40%, 9 in AF and 9 in SR) haemodynamics and BNP levels were measured from arterial and coronary sinus samples at baseline, after 10 min of 20 degrees passive head up tilt (HUT) and after 10 min of isometric handgrip (IHG) exercise. From these data, we calculated a transcardiac BNP gradient and compared results between the AF and SR cohort. RESULTS: During haemodynamic stress in both groups, there were no significance differences in left sided filling pressures. At baseline, there were no differences in BNP measurements between the SR and AF group. The transcardiac BNP gradient increased significantly in the SR (p=0.02) but not the AF cohort, after HUT. During IHG exercise, there was a significant decrease in cardiac BNP release in the AF cohort (p=0.03) but not the SR cohort. CONCLUSION: These data imply in HF, cardiac rhythm influences cardiac BNP release in response to haemodynamic stress.

Aged↗
PubMed2001

Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy.

BACKGROUND: Recent reports suggest that activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), in response to acute changes in cellular energy status in cardiac and skeletal muscles, results in altered substrate utilization. We hypothesized that chronic alterations in myocardial energetics in hypertrophied hearts (left ventricular hypertrophy, LVH) will lead to elevated AMPK activity, which in turn regulates substrate utilization. METHODS AND RESULTS: Using (31)P NMR spectroscopy and biochemical assays, we found that in LVH hearts, adenosine triphosphate (ATP) concentration decreased by 10%, phosphocreatine concentration decreased by 30%, and total creatine concentration was unchanged. Thus, the ratio of phosphocreatine/creatine decreased to one third of controls, and the ratio of AMP/ATP increased to 5 times above controls. These changes were associated with increased alpha(1) and alpha(2) AMPK activity (3.5- and 4.8-fold above controls, respectively). The increase in AMPK alpha(1) activity was accompanied by a 2-fold increase in alpha(1) expression, whereas alpha(2) expression was decreased by 30% in LVH. The basal rate of 2-deoxyglucose uptake increased by 3-fold in LVH, which was associated with an increased amount of glucose transporters present on the plasma membrane. CONCLUSIONS: These results demonstrate for the first time that chronic changes in myocardial energetics in hypertrophied hearts are accompanied by significant elevations in AMPK activity and isoform-specific alterations in AMPK expression. It also raises the possibility that AMPK signaling plays an important role in regulating substrate utilization in hypertrophied hearts.

AMP-Activated Protein Kinases↗
PubMed2000

Chloral hydrate versus midazolam for sedation of children for neuroimaging: a randomized clinical trial.

OBJECTIVE: The comparative safety and efficacy of chloral hydrate and midazolam for sedation of children has not been adequately studied. METHODS: In a double-blind randomized trial, at a single university hospital, we enrolled 40 children, ages 2 months to 8 years, in an out-patient neuroimaging study. Children judged to require sedation were enrolled during a 14-month period ending August 1995. They received identically appearing liquids of equal volume of either chloral hydrate (75 mg/kg, maximum 2 g) or midazolam (0.5 mg/kg, maximum 10 mg) by mouth. Children were monitored for changes in arterial blood pressure, oxygen saturation, pulse, respiration and anxiety. Efficacy was judged by evaluating the child's ability to complete the intended scan. Supplemental dosing was administered to children who were judged inadequately sedated 30 minutes after the initial medication. RESULTS: Interim analysis demonstrated a significant sedation failure rate. Of 40 enrolled children, 33 completed the protocol. Efficacy was significantly improved for the chloral hydrate group for both ability to perform the scan, chloral hydrate = 11/11 (100%, 95% CI = 72-100) vs. midazolam = 11/22 (50%, 95% CI = 29-71), and the need for supplementary dosing, chloral hydrate = 1/11 (9%, 95% CI = 0-26) vs midazolam = 12/22 (55%, 95% CI = 34-76), P<0.05. Mean duration of sedation was not significantly different. No physiological deterioration occurred and no oxygen administration was required. CONCLUSIONS: We conclude that, in these doses, oral chloral hydrate may provide more effective sedation than midazolam for brief neuroimaging studies in young children.

Anxiety↗
PubMed1996

Comparative review of the adverse effects of sedatives used in children undergoing outpatient procedures.

Children often fear medical procedures and interventions. Sedative agents enhance the care of these children who undergo outpatient procedures by decreasing anxiety, increasing cooperativity, and providing amnesia. Although higher dosages and intravenous administration of sedatives often produce improved sedation, adverse effects and complications are more frequent. The goals of therapeutic efficacy and safety must be balanced in all patients. The presence or anticipation of anxiety and pain helps in deciding whether to use a sedative alone, or a regimen also providing analgesia. The patient's clinical cardiorespiratory or neurological status, other relative contraindications, the duration of the intended procedure, and the presence or absence of an intravenous line will help in choosing specific drugs. Drug complications are a common cause of adverse events in patients. The combination of a sedative and analgesic, especially a benzodiazepine and an opioid given intravenously, is associated with a higher risk of serious complications. The practitioner responsible for the administration of a sedative to a child must be competent in its use and have the ability to detect and manage complications. Patients who are deeply sedated should be continuously monitored and observed by an individual dedicated to this task. Vital signs and oxygen saturation should be documented at frequent intervals and the patient should be appropriately monitored until discharge criteria have been met. The risk of serious complications with these agents may be reduced with vigorous monitoring and a judicious choice of dosage.

Ambulatory Care↗
PubMed1990

Circulating radioimmunoassayable inhibin during periods of transient follicle-stimulating hormone rise: secondary surge and unilateral ovariectomy.

We have measured changes in circulating immunoreactive (ir-) inhibin in male and female rats using an RIA with an antiserum raised against porcine inhibin alpha (1-26)-Gly-Tyr. The same synthetic peptide was used for standards and for the preparation of tracer. Serum ir-inhibin levels were significantly higher in intact female than in intact male rats (p less than 0.001). Immunoreactive inhibin was significantly reduced in both sexes 24 h after bilateral gonadectomy (p less than 0.0001). Unilateral ovariectomy (ULO) of female rats on metestrus caused a transient decrease in serum inhibin 8 h after surgery, but levels were not significantly different from those of sham-operated controls at later times after surgery. Increases in serum FSH and LH were observed for 8-18 h after ULO. Serum ir-inhibin levels were also measured on the early morning of estrus during the secondary FSH surge. At this time, ir-inhibin levels were low, while FSH levels were high and LH levels were low. These results show that serum ir-inhibin levels in rats are decreased at times when serum FSH levels are high.

Animals↗
PubMed1990

Differential effects of in vitro glucocorticoids on luteinizing hormone and follicle-stimulating hormone secretion: dependence on sex of pituitary donor.

We have used a dynamic perifusion system to determine whether glucocorticoids exert a direct effect on the secretion of LH and FSH from rat anterior pituitaries. Anterior pituitary fragments from male, proestrous female, or metestrous female rats were perifused for 8 h in either the absence (basal secretion rate) or presence of pulsatile GnRH administration (50 ng/ml peak concentration). Perifusions used medium containing 0.05% ethanol (vehicle), 600 ng/ml corticosterone, or 600 ng/ml cortisol. GnRH-stimulated secretion of FSH was enhanced in pituitaries from both male and female rats after in vitro incubation with either corticosterone or cortisol. The basal secretion rate of FSH was also elevated in proestrous females after glucocorticoid treatment. The GnRH-stimulated secretion rate for LH was significantly decreased in pituitaries from male rats treated with either glucocorticoid. In contrast, pituitaries from proestrous rats responded to either cortisol or corticosterone with an increase in LH secretion. Metestrous pituitaries showed divergent effects of the glucocorticoids on LH secretion; corticosterone enhanced secretion rates, and cortisol effected a decrease. Our data demonstrate that 1) glucocorticoids exert a direct effect on the secretion of LH and FSH from male and female rat pituitaries; 2) glucocorticoids elicit different effects on the secretion of LH and FSH, suggesting that they act at separate sites to regulate LH and FSH secretion; and 3) the effect of in vitro glucocorticoid treatment on gonadotropin secretion is dependent on sex and cycle stage of the pituitary donor and may be linked to prior in vivo concentrations of estrogen.

Animals↗
PubMed1990

Operative prostatomy: an aid to urethral anastomosis. A preliminary report.

Prostatomy is a technique that may be utilized during radical prostatectomy and bowel substitution for end stage bladder disease to preserve the urethral segment, thereby facilitating subsequent anastomosis. Although it is not applicable to all stages of prostate cancer, the technique involves a progressive longitudinal incision in the anterior prostate from the bladder neck to the proximal apex of the prostate until the divergence of the lateral lobes is visualized, thereby allowing precise identification of the entire supra-diaphragmatic urethra. This permits maximal preservation of the urethra to improve the likelihood of continence.

Anastomosis, Surgical↗
PubMed1989

Unilateral ovariectomy increases inhibin messenger ribonucleic acid levels in newly recruited follicles.

We have used the unilaterally ovariectomized (ULO) rat as an experimental model to assess transient relationships between follicular recruitment and inhibin mRNA levels in the ovary. Animals were divided into three experimental groups (ULO, sham-operated, and intact) and killed 0, 9, or 24 h postsurgery. Inhibin alpha- and beta A mRNA were measured within individual ovarian follicles by in situ hybridization. Serum FSH concentrations in ULO animals increased significantly at 9 h and returned to presurgery levels by 24 h. There was no effect of surgery on serum LH concentrations. In the ULO animals, compensatory follicular recruitment was observed in the remaining ovary at 24 h as a significant increase in the number of follicles with mean diameter greater than 350 micron. Two distinct populations of healthy maturing follicles, based on diameter and hybridization intensity, were observed in ovaries from 24 h post-ULO rats. The first class, NRF-1 (newly recruited follicle-1), were those recruited 48 h previously by the secondary FSH surge of the preceding cycle. These large follicles (greater than 500 micron mean diameter) hybridized to both inhibin probes. The second class of follicles (NRF-2), which represent those newly recruited by the ULO-induced increase in serum FSH, were smaller in size than NRF-1 (350-500 micron mean diameter). The intensity of hybridization of both inhibin probes to NRF-1 was higher than that to NRF-2 in the majority of follicles. Each NRF-1 contained higher levels of both alpha- and beta A-inhibin mRNA than nonrecruited follicles (150-350 micron diameter). These data suggest that subtle changes in serum FSH concentrations, which are sufficient to induce follicular recruitment into a size class capable of ovulating within a given cycle, play the additional role of enhancing inhibin mRNA levels in developing follicles.

Animals↗
PubMed1989

Decreased inhibin gene expression in preovulatory follicles requires primary gonadotropin surges.

We have examined the role of the primary gonadotropin surges in regulating inhibin alpha- and beta A-subunit mRNA levels in rat ovarian follicles. Inhibin subunit mRNA levels decline dramatically on the evening of proestrus in follicles of the ovulatory pool. Because this decline is temporally associated with primary gonadotropin surges, we investigated the contribution of LH and FSH to this process. The primary gonadotropin surges were blocked by injection of a GnRH antagonist (WY45760) at 1200 h on proestrus. This resulted in sustained elevation of inhibin mRNA levels through 0700 h of the subsequent day, a time when inhibin mRNA levels would normally be very low. Replacement of either exogenous LH or FSH in ovulatory doses to an antagonist-treated animal at 1530 h on proestrus resulted in a decrease in inhibin mRNA levels by 4-5 h postreplacement. We conclude that LH and FSH act via a common mechanism to repress inhibin mRNA levels in stimulated preovulatory follicles.

Animals↗
PubMed1988

Dynamic changes in inhibin messenger RNAs in rat ovarian follicles during the reproductive cycle.

The alterations in morphology and function of the ovarian follicle as it matures, ovulates, and becomes a corpus luteum are dramatic. A variety of steroid and polypeptide hormones influence these processes, and the ovary in turn produces specific hormonal signals for endocrine regulation. One such signal is inhibin, a heterodimeric protein that suppresses the secretion of follicle-stimulating hormone from pituitary gonadotrophs. Rat inhibin complementary DNA probes have been used to examine the levels and distribution of inhibin alpha-and beta A-subunit messenger RNAs in the ovaries of cycling animals. Striking, dynamic changes have been found in inhibin messenger RNA accumulation during the developmental maturation of the ovarian follicle.

Animals↗
PubMed1987

Cloning and nucleotide sequence analysis of complementary deoxyribonucleic acid for bovine preproinsulin.

A cDNA library was prepared from poly(A+) RNA isolated from fetal bovine pancreas. Bacterial colonies were screened for sequences homologous to a rat preproinsulin I cDNA probe. Ten positive clones were selected at random and further studied. Northern blot analyses revealed that seven of these clones hybridized to a single RNA species, of approximately 400 nucleotides. Sequence analysis of one of these clones (pbI2885) revealed the entire structural region of bovine preproinsulin mRNA including a 72 nucleotide region encoding a signal peptide enriched in hydrophobic residues. The overall nucleotide homology between bovine and human preproinsulin mRNA was 76% for the preregion, 89% for the A chain, 83% for the B chain, and 68% for the C peptide (including a 15 nucleotide deletion).

Amino Acid Sequence↗
PubMed1985

Ontogeny of immunoreactive insulin in the fetal bovine pancreas.

The aim of this study was to characterize the development of immunoreactive insulin (IRI) in the fetal bovine pancreas. Pancreatic IRI was acid extracted, and both pancreatic and serum IRI were quantitated by RIA. The amount of pancreatic IRI per wet tissue wt in first trimester fetuses was similar to that in the adult animal (8.2 +/- 0.7 and 5.9 +/- 1.7 U/g pancreas, respectively). IRI increased progressively during gestation, attaining 39.2 +/- 6.5 U/g pancreas in the third trimester, 7-fold higher than that in the adult. When pancreatic IRI concentrations were standardized for protein content of the extracts, a decrease was noted between the midsecond and third trimesters. This is most likely the result of dilution of the endocrine portion of the pancreas by the rapidly growing exocrine pancreas. IRI was also detectable in fetal sera from all three trimesters. In contrast to the profile for pancreatic concentrations of IRI, serum concentrations remained constant throughout gestation at approximately 20 microU/ml. Poly(A+)RNA was isolated from adult and fetal pancreata, and the relative levels of preproinsulin mRNA were assessed by DNA/RNA filter hybridization. There was a 2- to 3-fold increase in the relative level of preproinsulin mRNA in fetal pancreata between the first and second trimesters which was maintained through the third trimester. In the adult pancreas, preproinsulin mRNA levels were similar to those in the first trimester fetus. This profile for the ontogeny of pancreatic preproinsulin mRNA was similar to that for pancreatic IRI (units per pancreas) during fetal maturation. We conclude that in the bovine fetus: the endocrine pancreas synthesizes IRI during all three trimesters of development; pancreatic (units per g pancreas), but not serum, concentrations of IRI increase progressively as development proceeds; and the ontogeny of preproinsulin mRNA is paralleled by that of pancreatic IRI (units per pancreas).

Animals↗
PubMed1982

Role of thyroxine in coordinate control of corticosterone and CBG in postnatal development.

The role of thyroxine (T4) in the ontogeny of serum corticosteroid-binding globulin (CBG) and corticosterone has been studied in the rat. Daily injection of T4 (0.1 micrograms/g body wt) resulted in the precocious appearance of both CBG and corticosterone. A dose-response study revealed an increase in both CBG and corticosterone at thyroxine doses greater than 0.02 micrograms/g body wt. In propylthiouracil-induced hypothyroid pups, the developmental rise of both CBG and corticosterone was suppressed. To determine whether T4 elevation of CBG was mediated by corticosterone, serum CBG was measured in corticosterone-injected pups (10 micrograms/g body wt). No increase in CBG was detected on days 8 and 10. A slight increase, only one-eighth that elicited by T4, occurred on day 12. There was also no synergistic effect between T4 and corticosterone. We conclude that the postnatal increase in serum T4 concentrations cues the developmental rise of both CBG and corticosterone in the rat.

Aging↗
PubMed1982

Postnatal development of corticosteroid-binding globulin: effects of thyroxine.

The aim of this study was to examine the temporal and dose characteristics of the corticosteroid-binding globulin (CBG) response to T4 and to determine whether this response is due to stimulation of hepatic biosynthesis of CBG. When n-propylthiouracil (PTU)-induced hypothyroid pups were given a single injection of T4 (0.1 microgram/g BW) on postnatal day 5, 6, or 7, only pups treated on day 7 showed a significant increase in CBG. In a T4 dose-response study conducted with 5- and 8-day-old pups, older pups exhibited maximum CBG concentrations (Rmax) which were 2.5-fold higher than those of younger pups. The D1/2 (dose required to elicit half the maximum response) values were similar at both ages. The effect of T4 withdrawal on serum CBG was also studied in PTU-treated pups. T4 injection on postnatal days 5-19 resulted in a progressive rise in CBG. In pups treated with T4 on days 5-9 and then withdrawn from treatment through day 20, serum CBG showed no further increase but was maintained at an elevated level. Using a liver slice system to assess CBG production in vitro, livers from 14-day-old hyperthyroid pups produced 4.77 ng corticosterone bound/g liver, while livers from euthyroid pups produced no CBG. We conclude: 1) the response of CBG to T4 is a function of the age of the animal; between days 5 and 8 this is due to increased Rmax without any change in sensitivity to T4 (D1/2); 2) T4 is required not only to initiate but also to sustain the developmental increase in CBG; and 3) T4 elicits an increase in circulating CBG by stimulating its synthesis.

Aging↗